Scorpion beta-toxins and voltage-gated sodium channels: Interactions and effects

Frontiers in Bioscience

Volumn 18, Issue 2, 2013, Pages 572-587

  Escalona, Martha Pedraza ^a   Possani, Lourival D ^a  

^a INSTITUTO DE BIOTECNOLOGÍA   (Mexico)

Author keywords

Beta Scorpion Toxin; Bioactive surface; Review; Voltage Sensor Trapping Model; Voltage Gated Sodium Channel

Indexed keywords

GLUTAMIC ACID; NEUROTOXIN; SCORPION VENOM; VOLTAGE GATED SODIUM CHANNEL;

AMINO ACID SEQUENCE; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECT; HUMAN; INSECT; MAMMAL; METABOLISM; MOLECULAR GENETICS; PHYSIOLOGY; REVIEW; SCORPION; SEQUENCE ALIGNMENT;

AMINO ACID SEQUENCE; ANIMALS; GLUTAMIC ACID; HUMANS; INSECTS; MAMMALS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; NEUROTOXINS; SCORPION VENOMS; SCORPIONS; SEQUENCE ALIGNMENT; VOLTAGE-GATED SODIUM CHANNELS;

MLCS; MLOWN;

EID: 84878778505     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/4121     Document Type: Article

References (114)

1. Chippaux J.P. and M. Goyffon. Epidemiology of scorpionism: a global appraisal. Acta Trop. 107, 71-9 (2008)
2. Zeh D.W. The Biology of Scorpions. Polis G. A. Ed. Stanford University Press, Stanford, CA (1990)
3. Possani L.D., B. Becerril, M. Delepierre, J. Tytgat. Scorpion toxins specific for Na+-channels. Eur J Biochem 264, 287-300 (1999)
4. Tuuri R.E. and S. Reynolds. Scorpion envenomation and antivenom therapy. Pediatr Emerg Care 27, 667-72 (2011)
5. Brownell P., G.Polis. Scorpion Biology and Research- Introduction. Ed. Oxford Univiversity Press, New York (2001)
6. Catterall W.A., S. Cestèle, V. Yarov-Yarovoy, F.H. Yu, K. Konoki, T. Scheuer. Voltage-gated ion channels and gating modifier toxins. Toxicon 49, 124-41 (2007) (Pubitemid 46151715)
7. Jover E., F. Couraud, H. Rochat. Two types of scorpion neurotoxins characterized by their binding to two separate receptor sites on rat brain synaptosomes. Biochem Biophys Res Commun 95, 1607-14 (1980) (Pubitemid 11254309)
8. Couraud F., E. Jover, J.M. Dubois, H. Rochat. Two types of scorpion receptor sites, one related to the activation, the other to the inactivation of the action potential sodium channel. Toxicon 20, 9-16 (1982) (Pubitemid 12160499)
9. Imredy J. P. and R. MacKinnon. Energetic and structural interactions between delta-dendrotoxin and a voltage-gated potassium channel., J. Mol. Biol 296, 1283-1294 (2000)
10. Ruta V., R. MacKinnon. Localization of the voltagesensor toxin receptor on KvAP. Biochemistry 43, 10071-9 (2004)
11. Rodríguez de la Vega R. C., E. Merino, B. Becerril, L. D.Possani. Novel interactions between K+ channels and scorpion toxins. Trends in Pharmacological Sciences 24,222- 227 (2003). (Pubitemid 36588869)
12. Leipold E., A. Hansel, A. Borges, S.H. Heinemann. Subtype specificity of scorpion beta-toxin Tz1 interaction with voltage-gated sodium channels is determined by the pore loop of domain 3. Mol Pharmacol 70, 340-7 (2006)
13. Cestèle S., V. Yarov-Yarovoy, Y. Qu, F. Sampieri, T. Scheuer, W.A. Catterall. Structure and function of the voltage sensor of sodium channels probed by a betascorpion toxin. J Biol Chem 281,21332-44 (2006)
14. Cohen L., Y. Troub, M. Turkov, N. Gilles, N. Ilan, M. Benveniste, D. Gordon, M. Gurevitz. Mammalian skeletal muscle voltage-gated sodium channels are affected by scorpion depressant "insect-selective" toxins when preconditioned. Mol Pharmacol 72, 1220-7 (2007) (Pubitemid 350012596)
15. Diaz D., D.M. Delgadillo, E. Hernández-Gallegos, M.E. Ramírez-Domínguez, L.M. Hinojosa, C.S. Ortiz, J. Berumen, J. Camacho and J.C. Gomora. Functional expression of voltage-gated sodium channels in primary cultures of human cervical cancer. J Cell Physiol 210, 469- 78 (2007) (Pubitemid 44956892)
16. Catterall W.A., A.L. Goldin, S.G. Waxman. International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev 57, 397- 409 (2005) (Pubitemid 43036431)
17. Dong K. Insect sodium channels and insecticide resistance. Invert Neurosci 7, 17-30 (2007) (Pubitemid 46348843)
18. King G.F., P. Escoubas, G.M. Nicholson. Peptides toxins that selectively target insect Na(V) and Ca(V) channels. Channels (Austin) 2, 100-16 (2008).
19. Noda M., S. Shimizu, T. Tanabe, T. Takai, T, Kayano, T. Ikeda, H. Takahashi, H. Nakayama, Y. Kanaoka, N. Minamino. Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature 312, 121-7 (1984) (Pubitemid 14000075)
20. Duclohier H. Structure-function Studies on the voltagegated sodium channel. Biochim Biophys Acta. 1788, 2374-9 (2009)
21. Cestèle S., W.A. Catterall. Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie 82, 883-92 (2000)
22. Ragsdale D.S., J.C. McPhee, T. Scheuer, W.A. Catterall. Molecular determinants of state-dependent block of Na+ channels by local anesthetics. Science 265, 1724-8 (1994)
23. Stühmer W., F. Conti, H. Suzuki, X.D. Wang, M. Noda, N. Yahagi, H. Kubo, S. Numa. Structural parts involved in activation and inactivation of the sodium channel. Nature 339, 597-603 (1989) (Pubitemid 19174342)
24. West J.W., D.E. Patton, T. Scheuer, Y. Wang, A.L. Goldin, W.A. Catterall. A cluster of hydrophobic amino acids residues required for fast Na(+)-channel inactivation. Proc Natl Acad Sci U S A. 89,10910-4. (1992)
25. Broomand A. and F. Elinder. Large-scale movement within the voltage-sensor paddle of a potassium channelsupport for a helical-screw motion. Neuron 59, 770-7 (2008)
26. Lewis A., V. Jogini, L. Blachowicz, M. Lainé, B. Roux. Atomic constraints between the voltage sensor and the pore domain in a voltage-gated K+ channel of known structure. J Gen Physiol 131, 549-61 (2008) (Pubitemid 351749196)
27. Catterall W.A. Ion channel voltage sensors: structure, function, and pathophysiology. Neuron 67, 915-28 (2010)
28. Qu Y., R. Curtis, D. Lawson, K. Gilbride, P. Ge, P.S. DiStefano, I. Silos-Santiago, W.A. Catterall, T. Scheuer. Differential modulation of sodium channel gating and persistent sodium currents by the beta1, beta2 and beta3 subunits. Mol Cell Neurosci 18, 570-80 (2001) (Pubitemid 34008395)
29. Leterrier C., A. Brachet, M.P. Fache, B. Dargent. Voltage-gated sodium channel organization in neurons: protein interactions and trafficking pathways. Neurosci Lett 486, 92-100 (2010)
30. Kaczmarek L.K. Non-conducting functions of voltagegated ion channels. Nat Rev Neurosci 7, 761-71 (2006) (Pubitemid 44435259)
31. Gordon D., I. Karbat, N. Ilan, L. Cohen, R. Kahn, N. Gilles, K. Dong, W. Stühmer, J. Tytgat, M. Gurevitz. The differential preference of scorpion alpha-toxins for insect or mammalian sodium channels: implications for improved insect control. Toxicon 49, 452-472 (2007) (Pubitemid 46341388)
32. Rodríguez de la Vega R.C., L.D. Possani. Overview of scorpion toxins specific for Na+ channels and related peptides: biodiversity, structure-function relationships and evolution. Toxicon 46, 831-44 (2005) (Pubitemid 41735133)
33. Vazquez A., J.V. Tapia, W.K. Eliason, B.M. Martin, F. Lebreton, M. Delepierre, L.D. Possani, B. Becerril. Cloning and characterization of the cDNAs encoding Na+ channelspecific toxins 1 and 2 of the scorpion Centruroides noxius Hoffman. Toxicon 33, 1161-70 (1995)
34. Martin M.F., L.G. García y Pérez, M. el Ayeb, C. Kopeyan, G. Bechis, E. Jover, H. Rochat. Purification and chemical and biological characterizations of seven toxins from the Mexican scorpion, Centruroides suffusus suffusus. J Biol Chem 262, 4452-9 (1987)
35. Possani L.D., B.M. Martin, I. Svendsen, G.S. Rode, B.W. Erickson. Scorpion toxins form Centruroides noxius and Tityus serrulatus. Primary structures and sequence comparison by metric analysis. Biochem 229, 739-50 (1985) (Pubitemid 15243720)
36. Gordon D., N. Ilan, N. Zilberberg, N. Giles, D. Urbach, L. Cohen, I. Karbat, O. Froy, A. Gaathon, R.G. Kallen, M. Benveniste, M. Gurevitz. An 'Old World' scorpion beta-toxin that recognizes both insect and mammalian sodium channels. Eur J Biochem 270, 2663-70 (2003)
37. Pelhate M. and E. Zlotkin. Actions of insect toxin and other toxins derived form the venom of the scorpion Androctonus australis on isolated giant axons of the cockroach (Periplaneta americana). J Exp Biol 97, 67-77 (1982)
38. Zlotkin E., D. Kadouri, D. Gordon, M. Pelhate, M.F. Martin, H. Rochat. An excitatory and a depressant insect toxin from scorpion venom both affect sodium conductance and possess a common binding site. Arch Biochem Biophys 240, 877-87 (1985) (Pubitemid 15250056)
39. Froy O., N. Zilberberg, D. Gordon, M. Turkov, N. Gilles, M. Stankiewicz, M. Pelhate, E. Loret, D.A. Oren, B. Shaanan, M. Gurevitz. The putative bioactive surface of insect-selective scorpion excitatory neurotoxins. J Biol Chem 274, 5769-76 (1999) (Pubitemid 29109232)
40. Zuo X.P., Y.H. Ji. Molecular mechanism of scorpion neurotoxins acting on sodium channels: insight into their diverse selectivity.Mol Neurobiol 30, 265-78 (2004)
41. Gurevitz M., I. Karbat, L. Cohen, N. Ilan, R. Kahn, M. Turkov, M. Stankiewicz, W. Stühmer, K. Dong, D. Gordon. The insecticidal potencial of scorpion beta-toxins. Toxicon. 49, 473-89 (2007)
42. Catterall W.A. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26, 13-25 (2000)
43. Dutertre S., R.J. Lewis. Use of venom peptides to probe ion channel structure and function. J Biol Chem 285, 13315-20 (2010)
44. Restrepo-Angulo I., A. De Vizcaya-Ruiz, J. Camacho. Ion channels in toxicology. J Appl Toxicol 30, 497-512 (2010)
45. Possani L.D., E. Merino, M. Corona, F. Bolivar, B. Becerril. Peptides and genes coding for scorpion toxins that affect ion-channels. Biochimie 82, 861-8 (2000)
46. Wheeler K.P., D.D. Watt, M. Lazdunski. Classification of Na channel receptors specific for various scorpion toxins. Pflugers Arch 397, 164-5 (1983) (Pubitemid 13128857)
47. Roger J.C., Y. Qu, T.N. Tanada, T. Scheuer, W.A. Catterall. Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit. J Biol Chem 271, 15950-15962 (1996) (Pubitemid 26236206)
48. Bosmans F., J. Tytgat. Voltage-gated sodium channel modulation by scorpion alpha-toxins. Toxicon 49, 142-58 (2006)
49. Ulbricht W. Sodium channel inactivation: Molecular determinants and modulation. Physiol Rev 85, 1271-1301 (2005) (Pubitemid 41362271)
50. Cahalan M.D. Modification of sodium channel gating in frog myelinated nerve fibres by Centruroides sculpturatus scorpion venom. J Physiol 244, 511-34 (1975)
51. Meves H., N. Rubly, D.D. Watt. Effect of toxins isolated from the venom of the scorpion Centruroides sculpturatus on the Na currents of the node of Ranvier. Pflugers Arch 393, 56-62 (1982) (Pubitemid 12158971)
52. Campos F.V., B. Chanda, P.S. Beirão, F. Bezanilla. Beta-scorpion toxin modifies gating transitions in all four voltage sensors of the sodium channel. J Gen Physiol 130, 257-68 (2007) (Pubitemid 47443288)
53. Pinheiro C.B., S. Marangoni, M.H. Toyama, I. Polikarpov. Structural analysis of Tityus serrulatus Ts1 neurotoxin at atomic resolution: insights into interactions with Na+ channels. Acta Crystallogr, Sect D 59, 405-415 (2003) (Pubitemid 36360411)
54. Marcotte P., L.Q. Chen, R.G. Kallen, M. Chahine. Effects of Tityus serrulatus scorpion toxin gamma on voltage-gated Na+ channels. Circ Res 80, 363-9 (1997) (Pubitemid 27093350)
55. Cestèle S., Y. Qu, J.C. Rogers, H. Rochat, T. Scheuer, W.A. Catterall. Voltage sensor-trapping: enhanced activation of sodium channels by beta-scorpion toxin bound to the S3-S4 loop in domain II. Neuron 21, 919-31 (1998) (Pubitemid 28498798)
56. Bosmans F., M.F. Martin-Eauclaire, K.J. Swartz. Deconstructing voltage sensor function and pharmacology in sodium channels. Nature 456, 202-8 (2008)
57. Schiavon E., T. Sacco, R.R. Cassulini, G. Gurrola, F. Tempia, L.D. Possani, E. Wanke. Resurgent current and voltage sensor trapping enhanced activation by a beta-scorpion toxin solely in Nav1.6 channel. Significance in mice Purkinje neurons. J Biol Chem 281, 20326-37 (2006)
58. Schiavon E., M. Pedraza-Escalona, G.B. Gurrola, T. Olamendi-Portugal, G. Corzo, E. Wanke, L.D. Possani. Negative-shift activation, current reduction and resurgent currents induced by ?-toxins from Centruroides scorpions in sodium channels. Toxicon 59, 283-293 (2012)
59. Cannon S.C. and B.P. Bean. Sodium channels gone wild: resurgent current from neuronal and muscle channelopathies. J Clin Invest 120, 80-3 (2010)
60. Cestèle S., T. Scheuer, M. Mantegazza, H. Rochat, W.A. Catterall. Neutralization of gating charges in domain II of the sodium channel alpha subunit enhances voltage-sensor trapping by a beta-scorpion toxin. J Gen Physiol 118, 291-302 (2001)
61. Karbat I., N. Ilan, J.Z. Zhang, L. Cohen, R. Kahn, M. Benveniste, T. Scheuer, W.A. Catterall, D. Gordon, M. Gurevitz. Partial agonist and antagonist activities of a mutant scorpion beta-toxin on sodium channels. J Biol Chem 285, 30531-8 (2010)
62. Kaneda M., Y. Oyama, Y. Ikemoto, N. Akaike. Scorpion toxin prolongs an inactivation phase of the voltage-dependent sodium current in rat isolated single hippocampal neurons. Brain Res 487, 192-5 (1989) (Pubitemid 19135184)
63. Zhang Z., I. Karbat, L. Cohen, T. Scheuer, D. Gordon, M. Gurevitz, W. Catterall. Mapping the ?- scorpion toxin receptor site on voltage-gated sodium channels. Biophys J 98, 108a-109a (2010)
64. Zhang J.Z., V. Yarov-Yarovoy, T. Scheuer, I. Karbat, L. Cohen, D. Gordon, M. Gurevitz, W.A. Catterall. Structure-function map of the receptor site for ?-scorpion toxins in domain II of voltage-gated sodium channels. J Biol Chem 286, 33641-51 (2011)
65. Li C., R.J. Guan, Y. Xiang, Y. Zhang, D.C. Wang. Structure of an excitatory insect-specific toxin with an analgesic effect on mammals from the scorpion Buthus martensii Karsch. Acta Crystallogr D Biol Crystallogr 61, 14-21 (2005) (Pubitemid 41615527)
66. Karbat I., M. Turkov, L. Cohen, R. Kahn, D. Gordon, M. Gurevitz, F. Frolow. X-ray structure and mutagenesis of the scorpion depressant toxin LqhIT2 reveals key determinants crucial for activity and antiinsect selectivity. J Mol Biol 366, 586-601 (2007) (Pubitemid 46136199)
67. Pintar A., L. D. Possani, M. Delepierre. Solution structure of toxin 2 from Centruroides noxius Hoffmann, a beta-scorpion neurotoxin acting on sodium channels. J Mol Biol 287, 359-367 (1999) (Pubitemid 29141292)
68. Gordon D., H. Moskowitz, M. Eitan, C. Warner, W.A. Catterall, E. Zlotkin. Localization of receptor sites for insect-selective toxins on sodium channels by site-directed antibodies. Biochemistry 31, 7622-8 (1992)
69. Cohen L., I. Karbat, N. Gilles, O. Froy, G. Corzo, R. Angelovici, D. Gordon, M. Gurevitz. Dissection of the functional surface of the anti-insect excitatory toxin illuminates a putative "hot spot" common to all scorpion beta-toxins affecting Na+ channels. J Biol Chem 279, 8206-11 (2004) (Pubitemid 38294712)
70. Cohen L., I. Karbat, N. Gilles, N. Ilan, M. Benveniste, D. Gordon, M. Gurevitz. Common features in the surface of scorpion beta-toxins and elements that confer specificity for insect and mammalian voltage-gated sodium channels. J Biol Chem 280, 5045-53 (2005) (Pubitemid 40288680)
71. Karbat I., F. Frolow, O. Froy, N. Gilles, L. Cohen, M. Turkov, D. Gordon, M. Gurevitz. Molecular basis of the high insecticidal potency of scorpion alpha-toxins. J Biol Chem 279, 31679-86 (2004)
72. Estrada G., R. Restano-Cassulini, E. Ortiz, L.D. Possani, G. Corzo. Addition of positive charges at the Cterminal peptide region of CssII, a mammalian scorpion peptide toxin, improves its affinity for sodium channels Nav1.6. Peptides 32, 75-9 (2011)
73. Oren D.A., O. Froy, E. Amit, N. Kleinberger-Doron, M. Gurevitz, B. Shaanan. An excitatory scorpion toxin with a distinctive feature: an additional alpha helix at the C terminus and its implications for interaction with insect sodium channels. Structure 6, 1095-1103 (1998) (Pubitemid 28434113)
74. Gurevitz M., D. Gordon, S. Ben-Natan, M. Turkov, O. Froy. Diversification of neurotoxins by C-tail 'wiggling': a scorpion recipe for survival. FASEB J 15, 1201-5 (2001)
75. Cohen L., N. Lipstein, I. Karbat, N. Ilan, N. Gilles, R. Kahn, D. Gordon, M. Gurevitz. Miniaturization of scorpion beta-toxins uncovers a putative ancestral surface of interaction with voltage-gated sodium channels. J Biol Chem 283, 15169-76 (2008)
76. Tan P.T.J., S. Ranganathan, V. Brusic. Deduction of functional peptide motifs in scorpion toxins. J Peptide Sci 12, 420-427 (2006) (Pubitemid 43933230)
77. de Castro E., C.J.A. Sigrist, A. Gattiker, V. Bulliard, P.S. Langendijk-Genevaux, E. Gasteiger, A. Bairoch, N. Hulo. ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins. Nucleic Acids Res 34, W362-W365 (2006) (Pubitemid 44538121)
78. Combet C., C. Blanchet, C. Geourjon, G. Deléage. NPS@: network protein sequence analysis. Trends Biochem Sci 25, 147-50 (2000) (Pubitemid 30122428)
79. Glaser F., T. Pupko, I. Paz, R.E. Bell, D. Bechor- Shental. E. Martz, N. Ben-Tal. Consurf: identification of functional regions in proteins by surface-mapping of phylogenetic information. Bioinformatics 19, 163-4 (2003) (Pubitemid 36150199)
80. Pettersen E.F., T.D. Goddard, C.C. Huang, G.S. Couch, D.M. Greenblatt, E.C. Meng, T.E. Ferrin. UCSF Chimera - a visualization system for exploratory research and analysis. J Comput Chem 25, 1605-12 (2004)
81. Hernández-Salgado K., G. Estrada, A. Olvera, F.I. Coronas, L.D. Possani, G. Corzo. Heterologous expressed toxic and non-toxic peptide variants of toxin CssII are capable to produce neutralizing antibodies against the venom of the scorpion Centruroides suffusus suffusus. Immunol Lett 125, 93-9 (2009)
82. Canul-Tec J.C., L. Riaño-Umbarila, E. Rudiño-Piñera, B. Becerril, L.D. Possani, A. Torres-Larios. Structural basis of neutralization of the major toxic component from the scorpion Centruroides noxius Hoffmann by a humanderived single-chain antibody fragment. J Biol Chem 286, 20892-900 (2011)
83. Estrada G., B.I. García, E. Schiavon, E. Ortiz, S. Cestèle, E. Wanke, L.D. Possani, G. Corzo. Four disulfidebridged scorpion beta neurotoxin CssII: heterologous expression and proper folding in vitro. Biochim Biophys Acta 1770, 1161-8. (2007)
84. Strugatsky D., N. Zilberberg, M. Stankiewicz, N. Ilan, M. Turkov, L. Cohen, M. Pelhate, N. Gilles, D. Gordon, M. Gurevitz. Genetic polymorphism and expression of a highly potent scorpion depressant toxin enable refinement of the effects on insect Na channels and illuminate the key role of Asn-58. Biochemistry 44, 9179-87 (2005) (Pubitemid 40943232)
85. Barhanin J., M. Ildefonse, O. Rougier, S.V. Sampaio, J.R. Giglio, M. Lazdunski. Tityus gamma toxin, a high affinity effector of the Na+ channel in muscle, with a selectivity for channels in the surface membrane. Pflugers Arch 400, 22-7 (1984) (Pubitemid 14176550)
86. De Lima M.E., M.F. Martin, C.R. Diniz, H. Rochat. Tityus serrulatus toxin VII bears pharmacological properties of both beta-toxin and insect toxin from scorpion venoms. Biochem Biophys Res Commun 139, 296-302 (1986) (Pubitemid 16007275)
87. Hassani O., P. Mansuelle, S. Cestèle, M. Bourdeaux, H. Rochat, F. Sampiere. Role of lysine and tryptophan residues in the biological activity of toxin VII (Ts gamma) from the scorpion Tityus serrulatus. Eu J Biochem 260, 76- 86 (1999) (Pubitemid 29095697)
88. Borges A., M.J. Alfonzo, C.C. García, N.J. Winand, E. Leipold, S.H. Heinemann. Isolation, molecular cloning and functional characterization of a novel beta-toxin from the Venezuelan scorpion, Tityus zulianus. Toxicon 43, 671-84 (2004) (Pubitemid 38520771)
89. Bosmans F., M.F. Martin-Eauclaire, J. Tytgat. The depressant scorpion neurotoxin LqqIT2 selectively modulates the insect voltage-gated sodium channel. Toxicon 45, 501-7 (2005) (Pubitemid 40269940)
90. Gwee M.C.E., S. Nirthanan, H.E. Khoo, P. Gopalakrishnakone, R.M. Kini, L.S. Cheah. Autonomic effects of some scorpion venoms and toxins. Clin Exp Pharmacol Physiol 29, 795-801 (2002)
91. Clot-Faybesse O., C. Devaux, H. Rochat, R. Guieu. In vivo neurotoxicity of Androctonus australis hector scorpion venom: evidence that the supra-thoracic nervous system is not implicated in the clinical manifestations. Toxicon 39, 1003-7 (2001)
92. Bahloul M., A. Chaari, N. Khlaf-Bouaziz, L. Hergafi, H. Ksibi, H. Kallel, A. Chaari, H. Chelly, C. Ben Hamida, N. Rekik, M. Bouaziz. Gastrointestinal manifestations in severe scorpion envenomation. Gastroenterol Clin Biol 29, 1001-5 (2005)
93. Goyffon M., M. Vachon, N. Broglio. Epidemiological and clinical characteristics of the scorpion envenomation in Tunisia. Toxicon 20, 337-44 (1982)
94. Ismail M. The scorpion envenoming syndrome. Toxicon 33, 825-58 (1995)
95. Massensini A.R., T. Moraes-Santos, M.V. Gomez, M.A. Romano-Silva. Alpha and beta-scorpion toxins evoke glutamate release from rat cortical synaptosomes with different effects on [Na+]i and [Ca2+]i. Neuropharmacology 37, 289-97 (1998) (Pubitemid 28282634)
96. Fernandes V.M., A.R. Massensini, M.A. Prado, M.A. Silva, T. Moraes-Santos, M.V. Gomez. Effects of alpha-scorpion toxin, tityustoxin on the release of [3H] dopamine of rat brain prefrontal cortical slices. Neurochem Int 44, 91-97 (2004) (Pubitemid 37101385)
97. Gong J.P., R.M. Kini, M.C.E. Gwee, P.Gopalakrishnakone, M.C.M. Chung. Makatoxin I, a novel toxin isolated from the venom of the scorpion Buthus martensi Karsch, exhibits nitrergic actions. J Biol Chem 272, 8320-4 (1997)
98. Akaike H., M.C. Shin, C. Kubo, N. Akaike. Effects of scorpion toxin on excitatory and inhibitory presynaptic terminals. Toxicology 264, 198-204 (2009)
99. Fernandes V.M., R. Nicolato, T. Moraes-Santos, R.S. Gomez, M.A. Prado, M.A. Romano-Silva, M.V. Gomez. Beta-scorpion toxin induces the release of gamma-[3 H]aminobutyric acid in rat brain slices. Neuroreport 12, 2911-3 (2001).
100. Falqueto E.B., A.R. Massensini, T. Moraes-Santos, M.V. Gomez, M.A. Romano-Silva. Modulation of Na+- channels by neurotoxins produces different effects on [3H]Ach release with mobilization of distinct Ca2+- channels. Cell Mol Neurobiol 22, 819-26 (2002) (Pubitemid 36169228)
101. Fernandes V.M., M.A. Romano-Silva, D.A. Gomes, M.A. Prado, T.M. Santos, M.V. Gomez. Dopamine release evoked by beta scorpion toxin, Tityus gamma, in prefrontal cortical slices is mediated by intracellular calcium stores. Cell Mol Neurobiol 24.757-67 (2004)
102. Miranda D.M., M.A. Romano-Silva, E. Kalapothakis, C.R. Diniz, M.N. Cordeiro, T. Moraes-Santos, L. De Marco, M.A. Prado, M.V. Gomez. Spider neurotoxins block the beta scorpion toxin-induced calcium uptake in rat brain cortical synaptosomes. Brain Res Bull 54, 533-6 (2001) (Pubitemid 32496550)
103. Petricevich V.L. Scorpion venom and the inflammatory response. Mediators Inflamm. 2010, 903295 (2010)
104. Petricevich V.L., A. Hernández Cruz, F.I. Coronas, L.D. Possani. Toxin gamma from Tityus serrulatus scorpion venom plays an essential role in immunomodulation of macrophages. Toxicon 50, 66-75 (2007)
105. Petricevich V.L. Balance between pro- and antiinflammatory cytokines in mice treated with Centruroides noxius scorpion venom. Mediators Inflamm. 2006, 54273 (2006)
106. Lebrun I., V.L. Petricevich. Immunomodulatory effects of the Tityus serrulatus venom on murine macrophage functions in vitro. Mediator Inflamm. 2005, 39-49 (2005) (Pubitemid 40942909)
107. Petricevich V.L., E. Reynaud, A.H. Cruz, L.D. Possani. Macrophage activation, phagocitosis and intracellular calcium oscillations induced by scorpion toxins from Tityus serrulatus. Clin Exp Immunol 154, 415- 23 (2008)
108. Corrêa M.M., S.V. Sampaio, R.A. Lopes, L.C. Mancuso, O.A. Cunha, J.J. Franco, J.R. Giglio. Biochemical and histopathological alterations induced in rats by Tityus serrulatus scorpion venom and its major neurotoxin tityustoxin-I. Toxicon 35, 1053-67 (1997) (Pubitemid 27304192)
109. Daisley H., D. Alexander, P. Pitt-Miller. Acute myocarditis following Tityus trinitatis envenoming: morphological and pathophysiological characteristics. Toxicon 37, 159-65 (1999) (Pubitemid 28512995)
110. Gueron M., R.J. Adolph, I.L. Grupp, M. Gabel, G. Grupp, N.O. Fowler. Hemodynamic and myocardial consequences of scorpion venom. Am J Cardiol. 45, 979-86 (1980) (Pubitemid 10094481)
111. Teixeira A.L., B.F. Fontoura, L. Freire-Maia, C.R. Machado, E.R. Camargos, M.M. Teixeira. Evidence for a direct action of Tityus serrulatus scorpion venom on the cardiac muscle. Toxicon 39, 703-9 (2001)
112. Gueron M., R. Ilia, S. Sofer. The cardiovascular system alter scorpion envenomation. J Toxicol Clin Toxico. 30, 245-58 (1992)
113. Fletcher P.L., M.D. Fletcher, K. Weninger, T.E. Anderson, B.M. Martin. Vesicle-associated membrane proteína (VAMP) cleavage by a new metalloprotease from the Brazilian scorpion Tityus serrulatus. J Biol Chem 285, 7405-116 (2010)
114. Dehesa-Dávila M., L.D. Possani. Scorpionism and serotherapy in Mexico. Toxicon 32, 1015-8 (1994) (Pubitemid 24263681)